The mechanism of enzyme induction by 3', 5'-cyclic nucleotides will be studied in established tissue culture cell lines derived from rat liver or hepatomas. The induction of tyrosine aminotransferase by derivatives of cyclic AMP will be characterized further in HTC cells. This and other hepatoma cell lines will be examined for additional hepatic enzymes which respond to derivatives of cyclic AMP or cyclic GMP. Cellular components potentially involved in the inductions will be analyzed and compared among the various hepatoma cells and liver. The differences observed will be considered in relation to the differences in cellular responsiveness to cyclic nucleotides. Components being examined include cyclic nucleotide binding proteins and protein kinases together with proteins which modulate their activities. The functions of these proteins in enzyme inductions will be evaluated. BIBLIOGRAPHIC REFERENCES: C.W. Mackenzie III and R.H. Stellwagen, "Altered Interaction between Binding and Catalytic Subunits of a Cyclic AMP-stimulated Protein Kinase from Hepatoma Cells." Arch. Biochem. Biophys. In press. 1977. R.H. Stellwagen, K. Kohli, and R.D. Sailor, "The influence of Culture Conditions on the Induction of Tyrosine Aminotransferase by Cyclic Nucleotides in Rat Hepatoma Cells." J. Cell. Physiol. In press. 1977.